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Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response.

Cell reports (2019-03-21)
Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J Pallett, Thomas F Baumert, Mala Maini, Ariberto Fassati
ABSTRACT

In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a fundamental function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3' ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nuclei Isolation Kit: Nuclei EZ Prep, sufficient for 25 nuclei preparations (~1-10×107 cells/preparation)
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Anti-Actin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
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Anti-GAPDH antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
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Imidazolo-oxindole PKR inhibitor C16, ≥98% (HPLC)
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Anti-phospho-eIF2 α (pSer51) antibody produced in rabbit, affinity isolated antibody
Ficoll® Paque Plus, Cytiva 17-1440-02, pack of 6 × 100 mL

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